Phosphoproteome dynamics of streptomyces rimosus during submerged growth and antibiotic production

Ela Šarić, Gerry A. Quinn, Nicolas Nalpas, Tina Paradžik, Saša Kazazić, Želimira Filić, Maja Šemanjski, Paul Herron, Iain Hunter, Boris Maček, Dušica Vujaklija

Research output: Contribution to journalArticlepeer-review

Abstract

Streptomyces rimosus is an industrial streptomycete, best known as a producer of oxytetracycline, one of the most widely used antibiotics. Despite the significant contribution of Streptomyces species to the pharmaceutical industry, most omics analyses have only been conducted on the model organism Streptomyces coelicolor. In recent years, protein phosphorylation on serine, threonine, and tyrosine (Ser, Thr, and Tyr, respectively) has been shown to play a crucial role in the regulation of numerous cellular processes, including metabolic changes leading to antibiotic production and morphological changes. In this study, we performed a comprehensive quantitative (phospho)proteomic analysis during the growth of S. rimosus under conditions of oxytetracycline production and pellet fragmentation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis combined with phosphopeptide enrichment detected a total of 3,725 proteins, corresponding to 45.6% of the proteome and 417 phosphorylation sites from 230 phosphoproteins. Significant changes in abundance during three distinct growth phases were determined for 494 proteins and 98 phosphorylation sites. Functional analysis revealed changes in phosphorylation events of proteins involved in important cellular processes, including regulatory mechanisms, primary and secondary metabolism, cell division, and stress response. About 80% of the phosphoproteins detected during submerged growth of S. rimosus have not yet been reported in streptomycetes, and 55 phosphoproteins were not reported in any prokaryote studied so far. This enabled the creation of a unique resource that provides novel insights into the dynamics of (phospho)proteins and reveals many potential regulatory events during antibiotic production in liquid culture of an industrially important bacterium.

Original languageEnglish
Number of pages20
JournalmSystems
Volume7
Issue number5
Early online date12 Sep 2022
DOIs
Publication statusPublished - 26 Oct 2022

Keywords

  • streptomyces rimosus
  • oxytetracycline production
  • pellet fragmentation
  • proteome
  • phosphoproteome
  • peptide dimethylation labeling
  • oxytetracycline

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